A selective neurokinin-1 receptor antagonist in chronic PTSD: a randomized, double-blind, placebo-controlled, proof-of-concept trial

Eur Neuropsychopharmacol. 2011 Mar;21(3):221-9. doi: 10.1016/j.euroneuro.2010.11.012. Epub 2010 Dec 30.


The substance P-neurokinin-1 receptor (SP-NK(1)R) system has been extensively studied in experimental models of stress, fear, and reward. Elevated cerebrospinal fluid (CSF) SP levels were reported previously in combat-related PTSD. No medication specifically targeting this system has been tested in PTSD. This proof-of-concept randomized, double-blind, placebo-controlled trial evaluated the selective NK(1)R antagonist GR205171 in predominately civilian PTSD. Following a 2-week placebo lead-in, 39 outpatients with chronic PTSD and a Clinician-Administered PTSD Scale (CAPS) score ≥50 were randomized to a fixed dose of GR205171 (N=20) or placebo (N=19) for 8weeks. The primary endpoint was mean change from baseline to endpoint in the total CAPS score. Response rate (≥50% reduction in baseline CAPS) and safety/tolerability were secondary endpoints. CSF SP concentrations were measured in a subgroup of patients prior to randomization. There was significant improvement in the mean CAPS total score across all patients over time, but no significant difference was found between GR205171 and placebo. Likewise, there was no significant effect of drug on the proportion of responders [40% GR205171 versus 21% placebo (p=0.30)]. An exploratory analysis showed that GR205171 treatment was associated with significant improvement compared to placebo on the CAPS hyperarousal symptom cluster. GR205171 was well-tolerated, with no discontinuations due to adverse events. CSF SP concentrations were positively correlated with baseline CAPS severity. The selective NK(1)R antagonist GR205171 had fewer adverse effects but was not significantly superior to placebo in the short-term treatment of chronic PTSD. (ClinicalTrials.gov Identifier: NCT 00211861, NCT 00383786).

Trial registration: ClinicalTrials.gov NCT00211861 NCT00383786.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Double-Blind Method
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neurokinin-1 Receptor Antagonists*
  • Piperidines / adverse effects
  • Piperidines / therapeutic use*
  • Placebos
  • Psychiatric Status Rating Scales
  • Stress Disorders, Post-Traumatic / drug therapy*
  • Substance P / cerebrospinal fluid
  • Tetrazoles / adverse effects
  • Tetrazoles / therapeutic use*
  • Time Factors
  • Treatment Outcome
  • Young Adult


  • Neurokinin-1 Receptor Antagonists
  • Piperidines
  • Placebos
  • Tetrazoles
  • Substance P
  • vofopitant

Associated data

  • ClinicalTrials.gov/NCT00211861
  • ClinicalTrials.gov/NCT00383786